Extension Study (Extended Access) of Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic Stem Cell Transplant Recipients for the Treatment of Bronchiolitis Obliterans
| Status: | Recruiting |
|---|---|
| Conditions: | Bronchitis, Orthopedic, Pulmonary, Hematology |
| Therapuetic Areas: | Hematology, Pulmonary / Respiratory Diseases, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 10 - 80 |
| Updated: | 2/13/2019 |
| Start Date: | March 2, 2012 |
| End Date: | June 30, 2025 |
| Contact: | Nicole J Gormley, M.D. |
| Email: | nicole.gormley@nih.gov |
| Phone: | (240) 402-0210 |
Bronchiolitis Obliterans (BO) is an obstructive lung disease that can affect individuals that
have undergone a lung or hematopoietic stem cell transplant. BO has been studied most
extensively in lung transplant recipients, where it is considered to represent chronic lung
rejection. It is the leading cause of death after lung transplant, with mortality rates up to
55 percent. In hematopoietic stem cell transplantation, BO is thought to be a manifestation
of chronic graft-vs-host disease (GVHD). Up to 45 percent of patients undergoing
hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function.
Conventional therapy for patients who develop BO consists of augmentation of systemic
immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated
with deleterious consequences including increased risk of infections and decreased
graft-versus tumor/leukemia effects.
Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been
shown to improve overall survival and chronic rejection-free survival in lung transplant
patients. These findings suggest targeted delivery of immunosuppressive therapy to the
diseased organ warrants further investigation as this may minimize the morbidity associated
with systemic immunosuppression. However, there currently exists limited data regarding the
overall efficacy of inhaled cyclosporine to treat established BO following lung
transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of
BO following hematopoietic stem cell transplantation.
Here, we propose to evaluate the long-term safety and efficacy, of inhaled CIS for the
treatment of BO. Enrollment will be offered to subjects who have completed the end of study
(week 18 visit) for the initial protocol (Phase II Trial of CIS in lung transplant and
hematopoietic stem cell transplant recipients for treatment of Bronchiolitis Obliterans) and
who have shown evidence of benefit (either an improvement or stabilization) in BO/BOS with
CIS treatment.
Clinical parameters, including pulmonary function tests, will be measured in addition to
laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with
extended treatment with CIS will be recorded.
The primary objective is to provide long-term safety and efficacy data for the use of CIS in
hematopoietic transplant patients and lung transplant patients with established BO.
Secondary objectives include investigation of the inflammatory pathways that lead to chronic
BO and ascertainment of the long term anti-inflammatory effects of this CSA preparation ex
vivo and in vivo.
Primary endpoint is the efficacy of extended use CIS for BO/BOS. Secondary endpoints include
the toxicity profile (adverse events), improvement in high resolution chest CT images,
results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers
of inflammation, and functional capacity measurements using a six-minute walk test.
have undergone a lung or hematopoietic stem cell transplant. BO has been studied most
extensively in lung transplant recipients, where it is considered to represent chronic lung
rejection. It is the leading cause of death after lung transplant, with mortality rates up to
55 percent. In hematopoietic stem cell transplantation, BO is thought to be a manifestation
of chronic graft-vs-host disease (GVHD). Up to 45 percent of patients undergoing
hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function.
Conventional therapy for patients who develop BO consists of augmentation of systemic
immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated
with deleterious consequences including increased risk of infections and decreased
graft-versus tumor/leukemia effects.
Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been
shown to improve overall survival and chronic rejection-free survival in lung transplant
patients. These findings suggest targeted delivery of immunosuppressive therapy to the
diseased organ warrants further investigation as this may minimize the morbidity associated
with systemic immunosuppression. However, there currently exists limited data regarding the
overall efficacy of inhaled cyclosporine to treat established BO following lung
transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of
BO following hematopoietic stem cell transplantation.
Here, we propose to evaluate the long-term safety and efficacy, of inhaled CIS for the
treatment of BO. Enrollment will be offered to subjects who have completed the end of study
(week 18 visit) for the initial protocol (Phase II Trial of CIS in lung transplant and
hematopoietic stem cell transplant recipients for treatment of Bronchiolitis Obliterans) and
who have shown evidence of benefit (either an improvement or stabilization) in BO/BOS with
CIS treatment.
Clinical parameters, including pulmonary function tests, will be measured in addition to
laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with
extended treatment with CIS will be recorded.
The primary objective is to provide long-term safety and efficacy data for the use of CIS in
hematopoietic transplant patients and lung transplant patients with established BO.
Secondary objectives include investigation of the inflammatory pathways that lead to chronic
BO and ascertainment of the long term anti-inflammatory effects of this CSA preparation ex
vivo and in vivo.
Primary endpoint is the efficacy of extended use CIS for BO/BOS. Secondary endpoints include
the toxicity profile (adverse events), improvement in high resolution chest CT images,
results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers
of inflammation, and functional capacity measurements using a six-minute walk test.
Bronchiolitis Obliterans (BO) is an obstructive lung disease that can affect individuals that
have undergone a lung or hematopoietic stem cell transplant. BO has been studied most
extensively in lung transplant recipients, where it is considered to represent chronic lung
rejection. It is the leading cause of death after lung transplant, with mortality rates up to
55 percent. In hematopoietic stem cell transplantation, BO is thought to be a manifestation
of chronic graft-vs-host disease (GVHD). Up to 45 percent of patients undergoing
hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function.
Conventional therapy for patients who develop BO consists of augmentation of systemic
immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated
with deleterious consequences including increased risk of infections and decreased
graft-versus tumor/leukemia effects.
Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been
shown to improve overall survival and chronic rejection-free survival in lung transplant
patients. These findings suggest targeted delivery of immunosuppressive therapy to the
diseased organ warrants further investigation as this may minimize the morbidity associated
with systemic immunosuppression. However, there currently exists limited data regarding the
overall efficacy of inhaled cyclosporine to treat established BO following lung
transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of
BO following hematopoietic stem cell transplantation.
Here, we propose to evaluate the long-term safety and efficacy, of inhaled CIS for the
treatment of BO. Enrollment will be offered to subjects who have completed the end of study
(week 18 visit) for the initial protocol (Phase II Trial of CIS in lung transplant and
hematopoietic stem cell transplant recipients for treatment of Bronchiolitis Obliterans) and
who have shown evidence of benefit (either an improvement or stabilization) in BO/BOS with
CIS treatment.
Clinical parameters, including pulmonary function tests, will be measured in addition to
laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with
extended treatment with CIS will be recorded.
The primary objective is to provide long-term safety and efficacy data for the use of CIS in
hematopoietic transplant patients and lung transplant patients with established BO.
Secondary objectives include investigation of the inflammatory pathways that lead to chronic
BO and ascertainment of the long term anti-inflammatory effects of this CSA preparation ex
vivo and in vivo.
Primary endpoint is the efficacy of extended use CIS for BO/BOS. Secondary endpoints include
the toxicity profile (adverse events), improvement in high resolution chest CT images,
results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers
of inflammation, and functional capacity measurements using a six-minute walk test.
have undergone a lung or hematopoietic stem cell transplant. BO has been studied most
extensively in lung transplant recipients, where it is considered to represent chronic lung
rejection. It is the leading cause of death after lung transplant, with mortality rates up to
55 percent. In hematopoietic stem cell transplantation, BO is thought to be a manifestation
of chronic graft-vs-host disease (GVHD). Up to 45 percent of patients undergoing
hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function.
Conventional therapy for patients who develop BO consists of augmentation of systemic
immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated
with deleterious consequences including increased risk of infections and decreased
graft-versus tumor/leukemia effects.
Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been
shown to improve overall survival and chronic rejection-free survival in lung transplant
patients. These findings suggest targeted delivery of immunosuppressive therapy to the
diseased organ warrants further investigation as this may minimize the morbidity associated
with systemic immunosuppression. However, there currently exists limited data regarding the
overall efficacy of inhaled cyclosporine to treat established BO following lung
transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of
BO following hematopoietic stem cell transplantation.
Here, we propose to evaluate the long-term safety and efficacy, of inhaled CIS for the
treatment of BO. Enrollment will be offered to subjects who have completed the end of study
(week 18 visit) for the initial protocol (Phase II Trial of CIS in lung transplant and
hematopoietic stem cell transplant recipients for treatment of Bronchiolitis Obliterans) and
who have shown evidence of benefit (either an improvement or stabilization) in BO/BOS with
CIS treatment.
Clinical parameters, including pulmonary function tests, will be measured in addition to
laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with
extended treatment with CIS will be recorded.
The primary objective is to provide long-term safety and efficacy data for the use of CIS in
hematopoietic transplant patients and lung transplant patients with established BO.
Secondary objectives include investigation of the inflammatory pathways that lead to chronic
BO and ascertainment of the long term anti-inflammatory effects of this CSA preparation ex
vivo and in vivo.
Primary endpoint is the efficacy of extended use CIS for BO/BOS. Secondary endpoints include
the toxicity profile (adverse events), improvement in high resolution chest CT images,
results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers
of inflammation, and functional capacity measurements using a six-minute walk test.
- INCLUSION CRITERIA:
1. Completed the End of Study visit (week 19) on the initial protocol (Phase II
Trial of Cyclosporine Inhalation Solution (CIS) in Lung Transplant and
Hematopoietic Stem Cell Transplant Recipients for Treatment of Bronchiolitis
Obliterans) in the preceding 12 weeks
2. Patients have shown evidence for a clinical benefit to CIS as evidenced by one or
more of the following:
- Improvement in pulmonary function defined by a 10 percent or more increase in the FEV1
at week 18, confirmed with repeat PFTs at least 1 week apart.
- In patients with progressive disease at study entry on the initial protocol (Phase II
Trial of Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic
Stem Cell Transplant Recipients for Treatment of Bronchiolitis Obliterans),
stabilization in pulmonary function, defined as less than a 10 percent improvement in
FEV1 or less than 10 percent decline in FEV1 at week 18, confirmed with repeat PFTs at
least 1 week apart.
- In patients with stable disease (active BOS stable by FEV1 criteria) at study entry on
the initial protocol (Phase II Trial of Cyclosporine Inhalation Solution (CIS) in Lung
Transplant and Hematopoietic Stem Cell Transplant Recipients for Treatment of
Bronchiolitis Obliterans), stabilization in pulmonary function, defined as less than a
10 percent improvement in their FEV1 or less than 10 percent decline in FEV1, and a
decrease in the dose of one or more systemic immunosuppressants by at least 20 percent
(sustained for 3 weeks, excluding adjustments made for target drug levels). * The
criteria for study entry on this extension protocol are not the same as the criteria
for response on the primary protocol to allow for entry of patients on this extension
protocol, which is deriving some clinical benefit, but have not met the full response
criteria as defined in the primary protocol.
EXCLUSION CRITERIA:
1. More than a 12 week gap in study drug administration (CIS)
2. Evidence of uncontrolled, pulmonary infection
3. ECOG performance status greater than or equal to 3
4. Patient pregnant or breast feeding or not willing to continue the use of an approved
method of birth control
5. Life expectancy less than 18 weeks
6. History of hypersensitivity reaction to propylene glycol
7. Documented allergy or intolerance to CIS
8. History of untreated coronary insufficiency, severe cardiac arrhythmias, and/or
uncontrolled hypertension.
9. Serum creatinine greater than 2.5 mg/dl
10. Inability to comprehend the investigational nature of the study and provide informed
consent
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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